GABA_A receptor plasticity in Jurkat T cells

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• 作者：Leonardo Dionisio ; Ver贸nica Arias ; Cecilia Bouzat ; Mar铆a del Carmen Es ; i
• 关键词：GABAA receptors ; Lymphocytes ; Plasticity ; GABA
• 刊名：Biochimie
• 出版年：December, 2013
• 年：2013
• 卷：95
• 期：12
• 页码：2376-2384
• 全文大小：978 K

文摘

GABA_A receptors (GABA_AR) mediate inhibitory neurotransmission in the human brain. Neurons modify subunit expression, cellular distribution and function of GABA_AR in response to different stimuli, a process named plasticity. Human lymphocytes have a functional neuronal-like GABAergic system with GABA_AR acting as inhibitors of proliferation. We here explore if receptor plasticity occurs in lymphocytes. To this end, we analyzed human T lymphocyte Jurkat cells exposed to different physiological stimuli shown to mediate plasticity in neurons: GABA, progesterone and insulin. The exposure to 100聽渭M GABA differently affected the expression of GABA_AR subunits measured at both the mRNA and protein level, showing an increase of 伪1, 尾3, and 纬2 subunits but no changes in 未 subunit. Exposure of Jurkat cells to different stimuli produced different changes in subunit expression: 0.1聽渭M progesterone decreased 未 and 0.5聽渭M insulin increased 尾3 subunits. To identify the mechanisms underlying plasticity, we evaluated the Akt pathway, which is involved in the phosphorylation of 尾 subunits and receptor translocation to the membrane. A significant increase of phosphorylated Akt and on the expression of 尾3 subunit in membrane occurred in cells exposed 15聽h to GABA. To determine if plastic changes are translated into functional changes, we performed whole cell recordings. After 15聽h GABA-exposure, a significantly higher percentage of cells responded to GABA application when compared to 0 and 40聽h exposure, thus indicating that the detected plastic changes may have a role in GABA-modulated lymphocyte function.

Our results reveal that lymphocyte GABA_AR are modified by different stimuli similarly and by similar mechanisms to those in neurons. This property is of significance for the development of future therapies involving pharmacological modulation of the immune response.